Antcin K suppresses proinflammatory cytokines expression via the PI3K, Akt and NF-κB pathways in human gingival fibroblasts: implications for periodontitis treatment.

Numerous inflammatory cytokines control the pathogenesis of periodontitis, an infectious bacterial disease, via interacting with immune and tissue cells. Antrodia cinnamomea is the origin of the triterpenoid Antcin K, renowned for its immunomodulatory and anti-inflammatory properties. However, the therapeutic performances of Antcin K on periodontitis remain unclear. Lipopolysaccharide (LPS) is the primary virulence factor of Porphyromonas gingivalis, a common periodontal pathogen, which augments the synthesis of proinflammatory cytokines for instance IL-1β, IL-6, IL-8, and IL-17A in primary human gingival fibroblasts (HGFs). Interestingly, treatment of HGFs with Antcin K inhibited LPS-induced proinflammatory cytokines production. RNA sequencing analysis indicated that the PI3K-Akt pathway is potentially linked in Antcin K's anti-inflammatory function. We revealed that the PI3K, Akt, and NF-κB pathways mediate Antcin K's suppression of proinflammatory cytokines production. Specifically, our in vivo study demonstrated that Antcin K blocks pathogenesis of periodontal disease in a ligature-mediated periodontitis model. Therefore, we suggest that Antcin K may be a potential therapeutic candidate for controlling periodontal disease.